The invention relates generally to the fields of Raman spectroscopy and of analysis of particle size, morphology, and spatial distribution.
Surfaces form the interface between different physical and chemical entities, and the physical and chemical processes that occur at surfaces often control the bulk behavior of materials. For example, the rate of dissolution of drug particles in a biological fluid (e.g., stomach, intestinal, bronchial, or alveolar fluid in a human) can strongly influence the rate of uptake of the drug into an animal. Differences in particle size distribution between two otherwise identical compositions of the same drug can lead to significant differences in the pharmacological properties of the two compositions. Further by way of example, the surface area of a solid chemical catalyst can strongly influence the number and density of sites available for catalyzing a chemical reaction, greatly influencing the properties of the catalyst during the reaction. For these and other reasons, manufacturers often try to closely control particle size and shape. Associations between and among particles can also affect the pharmacological properties of substances in the particles, such as the ability of a substance to dissolve or become active in a biological system.
Numerous methods of analyzing particle sizes and distributions of particle sizes are known in the art, including at least optical and electron microscopy, laser diffraction, physical size exclusion, dynamic light scattering, polarized light scattering, mass spectrometric, sedimentation, focused beam backscattered light reflectance, impedance, radiofrequency migration, Doppler scattering, and other analytical techniques. Each of these techniques has a variety of limitations that preclude its use in certain situations. However, all of these techniques share a critical limitation that prevent effective use of the techniques for a wide variety of samples for which particle analysis would be valuable—namely, none of the prior art techniques is able to distinguish two particles that differ only in chemical composition. Put another way, a first particle having substantially the same size, shape, and weight as a second particle cannot be distinguished from the second particle in these methods. Furthermore, many prior art particle characterization methods depend on serial particle-by-particle analysis and are not suitable for analysis of multiple particles in parallel. The present invention overcomes these limitations.